Background: Several trials evaluated the role of intensive regimens, made of triplet chemotherapies plus bevacizumab, as first-line treatment for patients with metastatic colorectal cancer (mCRC). We previously reported, in a Phase II prospective study, the efficacy and the tolerability of FIrB/FOx regimen, reporting interesting results in terms of received dose intensities (rDIs) and safety.Methods: We reported a retrospective update of 85 patients treated with FIrB/FOx, an intensive regimen of 5-fluorouracil, bevacizumab, and weekly alternate irinotecan and oxaliplatin, to confirm its feasibility in “real life”. Subgroup analyses were performed, particularly among patients treated with standard and modified FIrB/FOx (based on age, performance status, and/or comorbidities).Results: Overall, 3-month objective response rate (ORR) and 6-month ORR were 75.9% and 55.3%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 14.4 and 34.9 months, respectively. Among the patients treated with standard and modified regimens, 3-month ORR, PFS, and OS were 75.8% and 76% (P=1.0000), 14.4 and 14.4 months (P=0.8589), and 37.8 and 26.6 months (P=0.7746), respectively. Among the K/NRAS wild-type and K/NRAS mutant patients, 3-month ORR, PFS, and OS were 95.2% and 74.5% (P=0.0526), 15.3 and 14.4 months (P=0.8753), and 37.8 and 51.4 months (P=0.8527), respectively. The rDIs were ≥80% of full doses both in the standard and in the modified regimens subgroups. Cumulative G3/4 toxicities were neutropenia (14.1%), diarrhea (17.6%), asthenia (9.4%), vomiting (5.6%), and hypertension (16.5%).Conclusion: This update shows that intensive regimens such as FIrB/FOx are also feasible options for first-line treatment of mCRC patients in the “real-life” setting.

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